Co-infection with multiple parasites is common in sub-Saharan Africa. Malaria and schistosomiasis are co-endemic diseases that affect nearly a billion people worldwide;89% of whom reside in Africa. These diseases impose an enormous public health burden individually, but little is known about the interactive effect that occurs with dual infection. Vaccines are urgently needed to eradicate these parasites yet vaccine development depends upon reproducing predictable host immune responses. Evidence suggests that patent helminth infection can alter host immune responses to acute protozoal infection. Our central hypothesis is that underlying helminthiasis, such as schistosomiasis, modulates the human immune response, affecting the incidence and severity of concomitant falciparum malaria. Prospective cohort field studies that we conducted in Mali, West Africa demonstrated age-specific protective effects in children with S. haematobium infection upon the time to acquisition of falciparum malaria, burden of malaria disease and geometric mean parasite density as compared to matched controls without schistosomiasis. Immunologic assays in sera and PBMC demonstrate alterations in Th-2 balance in children with helminth infection at the time of a malaria infection. Flow cytometry studies demonstrate marked increases in IL-4 production, predominantly by CD4+ central memory T cell (TCM) subsets, in children aged 4-8 years with schistosomiasis compared to matched controls. IL-4 is critical to memory induction in both the humoral arm the development of memory T cell responses. Using valuable samples that were collected during this clinical study, we will study the complex humoral and cell mediated immune responses that occur in response to malaria and assess differences in children with or without underlying schistosomiasis. We expect these studies to 1) demonstrate the importance of co-parasitic infections in the developing world and elucidate immunologic mechanisms that result in these clinical interactions, 2) provide insight into altered immune responses induced by polyparasitism that will be critical to malaria vaccine trial design, and 3) influence parasite treatment policies and control programs throughout much of the tropics. Our central aim is to examine the immunomodulatory effect that patent Schistosoma haematobium has upon the humoral and cellular response elicited to acute Plasmodium falciparum infection and how this immune response affects the incidence and severity of clinical malarial disease. We expect these studies to 1) demonstrate the importance of co-parasitic infections in the developing world and elucidate immunologic mechanisms that result in these clinical interactions, 2) provide insight into altered immune responses induced by polyparasitism that will be critical to malaria vaccine trial design, and 3) influence parasite treatment programs and preventative health policies throughout much of the tropics.